Tissue samples were taken from the gastrocnemius muscle of 26 randomly selected, glucose-tolerant, 48-yr-old men. Hexokinase, phosphorylase, lactate dehy-drogenase (LDH), succinate dehydrogenase, and lipo-protein lipase activity (LPLA), as well as the area per fiber type and capillary density, were determined. Mean fiber area correlated positively with relative body weight (r = 0.53, P < 0.01), but capillary density did not. The result is that, in cases of high body weight, each capillary supplies a larger muscle fiber area. Serum insulin concentration in the fasting state correlated positively with body weight (r = 0.77, P < 0.001) and with mean fiber area per capillary (r = 0.87; P < 0.001). Only during the latter part of an oral glucose tolerance test (OGTT) did blood glucose concentrations correlate with relative body weight and mean fiber area per capillary (r = 0.42, r = 0.51, P < 0.05). A stepwise multiple regression analysis showed that the different muscle morphology measurements could account for % of the variation in the fasting serum Insulin concentration, the fasting insulin/glucose ratio, and the blood glucose concentration at 120 min in the OGTT. Of the intracellular enzymes, only LDH (r = -0.71, P < 0.001) correlated with the mean fiber area per capillary. LPLA correlated with capillary density (r = 0.66, P < 0.001), and, along with the muscle morphology measurements, could account for ¾ of the variation in serum triglyceride concentrations. The results show that a large mean muscle fiber area/capillary ratio indicates a morphologic imbalance, which is related to both glucose tolerance and various degrees of insulin sensitivity.